A Dual-Action Armed Replicating Adenovirus for the Treatment of Osteoblastic Bone Metastases of Prostate Cancer

Abstract

We hypothesize that the efficacy of a replicating adenovirus for the treatment of bone metastases of prostate cancer could be enhanced by arming it with the therapeutic protein sOPG-Fc which will block osteoclastic bone resorption and hence inhibit bone remodeling. Thus we constructed a dual-action armed replicating adenovirus expressing sOPG-Fc designed to both directly kill metastatic prostate cancer cells by oncolysis and also secrete sOPG-Fc into the microenvironment of the bone thereby inhibiting osteoclastic bone resorption. We have shown that the sOPG-Fc gene is expressed in a similar temporal manner to the E3B genes which it replaced and that the remaining E3 genes continue to be expressed. We have confirmed that expression of sOPG-Fc does not impair the selectivity or oncolytic potency of the armed replication-selective adenovirus. We have confirmed that the armed replicating adenovirus can simultaneously eradicate prostate cancer cells by oncolysis and inhibit osteoclast formation in vitro.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2007
Accession Number
ADA473269

Entities

People

  • Joanne T. Douglas

Organizations

  • University of Alabama

Tags

DTIC Thesaurus Topics

  • Adenoviruses
  • Biological Factors
  • Blood
  • Bone And Bones
  • Bone Diseases
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Lymphocytes
  • Macrophages
  • Microbiology
  • Neoplasms
  • Peptides
  • Prostate Cancer
  • Proteins
  • Viral Structures
  • Virology

Fields of Study

  • Biology

Readers

  • Marine Ecotoxicology
  • Oncology (Cancer Research).